Objective: To investigate the inhibitory effect of paclitaxel on hepatic fibrosis induced by bovine serum albumin (BSA) in rats and its mechanism.
Methods: Wistar rats after the formation of immunological liver fibrosis induced by BSA, were injected with normal saline (model group) or 10 μg/g paclitaxel (paclitaxel treatment group) via tail vein respectively, and another 10 normal rats administered with normal saline with the same fashion were served as control group. Injection was performed once daily, and the rats were sacrificed and their blood samples and liver specimens were obtained 28 d later, and then histopathological observations were performed, the serum biochemical parameters for liver function and the collagen-related variables in the serum and liver tissue, and the expressions of α-SMA and TGF-β1 in the liver tissue were measured; the hepatic stellate cells (HSCs) were isolated, and then the protein and mRNA expressions of molecules related to TGF-β/Smad signaling pathway in them were determined.
Results: In model group compared with control group, significant liver fibrosis was present, the levels of serum transaminases were significantly increased with significantly decreased albumin level, the collagen-related variables in the serum and liver tissue were significantly augmented, the expression rates of α-SMA and TGF-β1 in the liver tissue were significantly elevated, and the protein and mRNA expressions of molecules related to TGF-β/Smad signaling pathway in the HSCs were significantly up-regulated (all P<0.05). The changing amplitudes of all above variables in paclitaxel treatment group were significantly lower than those in model group (all P<0.05), and some of them showed no significant differences with control group (partial P<0.05).
Conclusion: Paclitaxel has inhibitory effect on immunological liver fibrosis induced by BSA in rats, and the mechanism may probably associated with its suppressing the activity of the TGF-β/Smad signaling pathway.